Peripheral Nervous System

Pain

Pain Sensation

Pain is an unpleasant sensation caused by the activation of nociceptors by thermal, mechanical, chemical, or other stimuli.

Learning Objectives

Describe the sensation of pain in the peripheral nervous system

Key Takeaways

Key Points

Sleeping or silent nociceptors do not respond to these types of signals, but may respond during inflammation of the surrounding tissue.

Nociceptors receive and send pain signals through myelinated fast Aδ fibers and nonmyelinated slow C fibers that are only activated with intense or prolonged input.

Nociceptive pain may also be divided into visceral, deep somatic, and superficial somatic pain.

Neuropathic pain is caused by damage to the nervous system.

Phantom pain is pain perceived as from amputated or paralyzed limbs.

Psychogenic pain is caused or exacerbated by mental, emotional, and behavioral factors.

Key Terms

visceral: Relating to the internal organs.

ischemia: A restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism.

pain: An ache or bodily suffering, or an instance of this; an unpleasant sensation, resulting from a derangement of functions, disease, or injury by violence; hurt.

nociceptor: A sensory receptor that sends signals that cause the perception of pain in response to a potentially damaging stimulus.

Overview

Pain is an unpleasant feeling often caused by intense or damaging stimuli, such as stubbing a toe, burning a finger, putting alcohol on a cut, and bumping the funny bone. The International Association for the Study of Pain’s widely used definition states: “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”

Pain motivates the individual to withdraw from damaging situations, to protect a damaged body part while it heals, and to avoid similar experiences in the future. Most pain resolves promptly once the painful stimulus is removed and the body has healed, but sometimes pain persists despite removal of the stimulus and apparent healing of the body. Pain sometimes arises in the absence of any detectable stimulus, damage, or disease.

Nociceptors

A nociceptor is a sensory receptor that responds to potentially damaging stimuli by sending nerve signals to the spinal cord and brain. This process, called nociception, usually causes the perception of pain. There are several types and functions of nociceptors:

Thermal nociceptors are activated by noxious heat or cold at various temperatures.

Mechanical nociceptors respond to excess pressure or mechanical deformation. They also respond to incisions that break the skin surface. These mechanical nociceptors frequently have polymodal characteristics. So it is possible that some of the transducers for thermal stimuli are the same for mechanical stimuli.

Chemical nociceptors respond to a wide variety of spices commonly used in cooking. The one that sees the most response and is very widely tested is capsaicin. Other chemical stimulants are environmental irritants like acrolein, a World War I chemical weapon and a component of cigarette smoke. Besides these external stimulants, chemical nociceptors have the capacity to detect endogenous ligands, and certain fatty acid amines that arise from changes in internal tissues.

The peripheral terminal of the mature nociceptor is where the noxious stimuli are detected and transduced into electrical energy. When the electrical energy reaches a threshold value, an action potential is induced and driven towards the central nervous system. This leads to the train of events that allows for the conscious awareness of pain.

Gray matter in the spinal cord: A delta fibers (Aδ fibers), a type of sensory fiber, are associated with the sensation of cold and pressure. Aδ fibers are thinly myelinated; therefore, they conduct signals more rapidly than unmyelinated C fibers, but more slowly than other, more thickly myelinated “A” class fibers. Aδ fibers terminate at Rexed laminae I and V (labeled I and V in the diagram). C fibers respond to thermal, mechanical, and chemical stimuli and terminate at the Rexed lamina II (labeled II in the diagram).

Nociceptors have two different types of axons.

The Aδ fiber axons are myelinated and can allow an action potential to travel at a rate of about 20 meters/second towards the central nervous system.

The other type is the more slowly conducting C fiber axons. These only conduct at speeds of around 2 meters/second. This is due to the light or nonmyelination of the axon.

Phases of Pain

Pain comes in two phases. The first phase is mediated by the fast-conducting Aδ fibers, and the second part is due to C fibers. The pain associated with the Aδ fibers can be associated to an initial extremely sharp pain.

The second phase is a more prolonged and slightly less intense feeling of pain as a result of the damage. If there is massive or prolonged input to a C fiber, there is a progressive build up in the spinal cord dorsal horn; this phenomenon is similar to tetanus in muscles but is called wind-up. If wind-up occurs, there is a probability of increased sensitivity to pain.

Although each nociceptor can have a variety of possible threshold levels, some do not respond at all to chemical, thermal, or mechanical stimuli unless injury actually has occurred. These are typically referred to as silent or sleeping nociceptors since their response comes only at the onset of inflammation to the surrounding tissue.

Types of Nociceptive Pain

Nociceptive pain can be divided into visceral, deep somatic and superficial somatic pain.

Visceral structures are highly sensitive to stretch, ischemia, and inflammation, but relatively insensitive to other stimuli that normally evoke pain in other structures, such as burning and cutting. Visceral pain is diffuse, difficult to locate, and often referred to a distant, usually superficial, structure. It may be accompanied by nausea and vomiting and may be described as sickening, deep, squeezing, and dull.

Deep somatic pain is initiated by stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fasciae and muscles, and is a dull, aching, poorly localized pain. Examples include sprains and broken bones.

Superficial pain is initiated by the activation of nociceptors in the skin or other superficial tissue, and is sharp, well-defined, and clearly located. Examples of injuries that produce superficial somatic pain include minor wounds and minor (first degree) burns.

Localization of Pain

Localization of pain is determined by whether the pain is superficial somatic, visceral, or deep somatic.

Learning Objectives

Describe the localization of pain in the peripheral nervous system

Key Takeaways

Key Points

Nociceptive pain is caused by stimulation of peripheral nerve fibers that respond only to stimuli approaching or exceeding harmful intensity ( nociceptors ).

Nociceptive pain may be classified according to the mode of noxious stimulation, the most common categories being thermal (heat or cold), mechanical (crushing, tearing, etc.), and chemical (iodine in a cut, chili powder in the eyes).

Superficial pain is initiated by activation of nociceptors in the skin or other superficial tissue, and is sharp, well-defined, and clearly located.

Visceral pain is diffuse and difficult to locate; deep somatic pain is dull aching and difficult to locate; and superficial somatic pain is sharp, well-defined, and easily located.

Referred pain is characterized by pain felt in a location away from the site of the painful stimulus.

Key Terms

visceral pain: Visceral pain is diffuse, difficult to locate, and often referred to a distant, usually superficial, structure. It may be accompanied by nausea and vomiting and may be described as sickening, deep, squeezing, and dull.

superficial somatic pain: Pain initiated by activation of nociceptors in the skin or other superficial tissue; it is sharp, well-defined, and clearly located. Examples of injuries that produce superficial somatic pain include minor wounds and minor (first degree) burns.

Pain Categories

Nociceptive pain is caused by stimulation of peripheral nerve fibers that respond only to stimuli approaching or exceeding harmful intensity (nociceptors), and may be classified according to the mode of noxious stimulation.

The most common categories are thermal (heat or cold), mechanical (crushing, tearing, etc.), and chemical (iodine in a cut, chili powder in the eyes). Nociceptive pain may also be divided into visceral, deep somatic, and superficial somatic pain.

Visceral Pain

Visceral structures are highly sensitive to stretch, ischemia, and inflammation, but relatively insensitive to other stimuli that normally evoke pain in other structures, such as burning and cutting. Visceral pain is diffuse, difficult to locate, and often referred to a distant, usually superficial, structure. It may be accompanied by nausea and vomiting and may be described as sickening, deep, squeezing, and dull.

Deep Somatic Pain

Deep somatic pain is initiated by the stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fasciae, and muscles, and is a dull, aching, poorly localized pain. Examples include sprains and broken bones. Superficial pain is initiated by activation of nociceptors in the skin or other superficial tissue, and is sharp, well-defined, and clearly located. Examples of injuries that produce superficial somatic pain include minor wounds and minor (first degree) burns.

Referred Pain

Referred pain (also reflective pain) is pain perceived at a location other than the site of the painful stimulus. An example is the case of ischemia brought on by a myocardial infarction ( heart attack), where pain is often felt in the neck, shoulders, and back rather than in the chest, the site of the injury.

The International Association for the Study of Pain has not officially defined referred pain as of 2001; hence, several authors have defined the term differently. Radiation is different from referred pain.

The pain related to a myocardial infarction could either be referred pain or pain radiating from the chest. Classically, the pain associated with a myocardial infarction is located in the middle or left side of the chest, where the heart is actually located. The pain can radiate to the left side of the jaw and into the left arm.

Referred pain occurs when the pain is located away from or adjacent to the organ involved. An example would be when a person has pain only in their jaw or left arm, but not in the chest. The size of referred pain is related to the intensity and duration of ongoing/evoked pain.

Also, temporal summation is a potent mechanism for the generation of referred muscle pain. Central hyperexcitability is also important for the extent of referred pain.

Temporal summation: Temporal summation, shown in the diagram, is the transmitting of signals with increased frequency of impulse, thus increasing the strength of signals in each fiber. Temporal summation is a potent mechanism for the generation of referred muscle pain.

Brain freeze: In an ice cream headache, known colloquially as brain freeze and medically as a cold-stimulus headache, the trigeminal nerve, shown in yellow, conducts signals from dilating blood vessels in the palate to the brain that interpret the pain as coming from the forehead.